The focus of the proposed UCLA Pharmacogenetics and Pharmacogenomics Research Group (PPRG) is the pharmacogenetics and pharmacogenomics of depression in Mexican-Americans. Depression is a common, complex disorder of unknown cause that affects 15 percent of the population, costing over 40 billion dollars to the U.S. economy annually. The pharmacogenetics of depression is therefore of great relevance to public health. The UCLA PPRG will study the clinical pharmacogenetics of antidepressant treatment response in Mexican-Americans. This specific aim will be addressed by a complementary project. Project 1 (specific aim 1) examines phenotype-genotype interactions in 800 Mexican-Americans subjects suffering from major depression. This will be a double-blind, randomized 8-week trial of two antidepressant drugs, one predominantly serotoninergic and the other predominantly norepinephrinergic; 400 patients will be assigned randomly to each drug. We will verify whether polymorphisms of relevant candidate genes are associated with treatment response. Clinical data and DNA obtained in this study will be deposited in the proposed UCLA PPRG DNA Bank, to become a national resource that will be available to other research groups. This project will be developed at UCLA by a cohesive, cross-disciplinary group of expert investigators that can utilize the data generated within the UCLA PPRG to inform and enrich the project. This ability to go from molecule to man, using the tools of contemporary biology to generate a coherent and synergist body of work that integrates pharmacogenetic and pharmacogenomic research at the genetic, molecular, cellular, integrative, behavioral, clinical levels is a key feature of the UCLA PPRG. Our data will be deposited in the NIGMS pharmacogenetics database.